DESCRIPTION (from the application): Metalloproteases and integrins are known to mediate interactions of endothelial cell (ECs) with matrix proteins through matrix degradation and cell adhesion events. Thus these molecules play important roles angiogenesis, a process that is essential in normal physiological processes such as embryonic development and wound healing, as well as in many diseases such as rheumatoid arthritis, atherosclerosis, tumor growth and eye ailments. A new family of mammalian cell surface proteins, called ADAMs (A Disintegrin And Metalloprotease Domain), share structural and functional characteristics of several types of metalloproteases; what makes the ADAM proteins especially intriguing is that they also contain a disintegrin domain which is a potential integrin binding ligand. Although exhibiting this dual function, the ADAMs have never been studied with regard to their role in angiogenesis. We hypothesize that the ADAMs participate in angiogenesis. We further propose that during angiogenesis, ADAMs can bind to integrin adhesion receptors and localize proteases activity at the site of cellular adhesion. The intent of this application is to identify ADAM(s) that modulate in vitro EC capillary formation in Matrigel, a model system that mimics angiogenesis. We plan to amplify ADAMs from human endothelial cells by homology PCR; We will also clone full length ADAMs that are specifically responsive to EC capillary formation. We will study the correlation between ADAM mRNA and protein expression and capillary formation; We will also explore the involvement of ADAMs in capillary formation by using potential integrin-binding peptides derived from the disintegrin sequences and the blocking monoclonal antibodies raised against the specific ADAMs. This study will provide valuable data to understand the regulation of angiogenesis by EC surface molecules, the ADAMs.